Plexin-B1 safeguards astrocyte agility and glial alignment to facilitate wound corralling and axon pathfinding after spinal cord injury

Glial spatial organization is critical for neural repair after spinal cord injury (SCI). In response to injury, reactive astrocytes extend hypertrophic processes to corral the lesion core and sequester debris and inflammatory cells. How these long, arborized processes remain intact, and how astrocytes avoid collisions to assemble a glial bridge to guide axon pathfinding across lesion site remain unclear. Here we identify the guidance receptor Plexin‑B1 as a key regulator of membrane integrity, process plasticity, and astrocyte alignment. Live‑cell imaging revealed that Plexin‑B1 deletion triggers membrane shedding and slows extension and retraction of astrocytic processes. The loss of astrocyte agility disrupts contact‑dependent avoidance, leading to disorganized astrocytes and misguided axons in vitro and in vivo. Mice with astrocyte‑specific Plexin‑B1 deletion showed defective glial border, enlarged lesions, inflammatory spill‑over, and dysregulated astrocyte–microglia signaling. These defects resulted in impaired axon regeneration and poorer functional recovery after spinal‑cord injury. Thus, Plexin‑B1 mediated agility of astrocyte processes safeguards membrane integrity and spatial alignment, enabling effective wound corralling and axon pathfinding during neural repair following SCI.